Bile Acid Metabolism in Liver Diseases

Bile acids are amphipathic molecules synthesised in hepatocytes from cholesterol and secreted into the bile canaliculi to facilitate lipid digestion and absorption. Beyond their detergent function, bile acids act as signalling ligands for nuclear and membrane receptors, notably the farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (TGR5). In healthy physiology, a tightly regulated enterohepatic circulation maintains bile acid homeostasis through coordinated uptake by the apical sodium-dependent bile acid transporter in enterocytes, hepatic uptake via the sodium-taurocholate cotransporting polypeptide (NTCP), and export through the bile salt export pump (BSEP). Dysregulation of these pathways contributes to the pathogenesis of a spectrum of liver diseases. In cholestatic conditions, impaired canalicular excretion leads to intrahepatic accumulation of hydrophobic bile acids, triggering hepatocyte injury, inflammation and fibrosis. In non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), alterations in bile acid synthesis, pool composition and receptor signalling have been implicated in insulin resistance, lipid dysmetabolism and fibrogenesis. Cross-talk between the gut microbiota and bile acid pool further modulates hepatic injury, with microbial enzymes converting primary bile acids to secondary species that exert distinct receptor-mediated effects. Advances in understanding these interconnections have spurred development of bile acid-targeted therapies, such as FXR agonists and bile acid sequestrants, offering new avenues to attenuate liver injury and improve metabolic outcomes.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Bile Acid Metabolism in Liver Diseases publication trend

The graph below shows the total number of articles in bile acid metabolism in liver diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Bile acids: Cholesterol-derived amphipathic molecules that emulsify dietary lipids and act as signalling ligands for receptors such as FXR and TGR5.

Farnesoid X receptor (FXR): A nuclear receptor activated by bile acids that regulates genes involved in bile acid synthesis, transport, lipid and glucose metabolism.

Enterohepatic circulation: The recycling loop in which bile acids secreted into the intestine are reabsorbed and transported back to the liver.

Non-alcoholic fatty liver disease (NAFLD): A condition characterised by excess hepatic fat accumulation not attributable to alcohol, encompassing a spectrum from simple steatosis to non-alcoholic steatohepatitis and fibrosis.

References

1. Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism. npj Biofilms and Microbiomes (2023).
2. Association of Serum and Fecal Bile Acid Patterns With Liver Fibrosis in Biopsy-Proven Nonalcoholic Fatty Liver Disease: An Observational Study. Clinical and Translational Gastroenterology (2022).
3. Berberine Alleviates Non-alcoholic Steatohepatitis Through Modulating Gut Microbiota Mediated Intestinal FXR Activation. Frontiers in Pharmacology (2021).